Basic research on anti-tumor effects of Interferon-α on hepatocellular carcinoma

点击翻译按钮获取中文摘要

[Purpose] In this study, we examined that the effects of IFN-α subtypes on the growth of human liver cancer cell lines in vitro ; growth inhibitory effects of IFN-α and 5-Fu in vitro ; mechanisms of apoptosis induction by IFN-α; and the effects of IFN-α alone or IFN-α plus 5-Fu on the growth of human liver cancer cell lines transplanted In nude mice.[Results] 1. When we examined the effects of five kinds of recombinant IFN-α subtypes (α1, α2, α5, α8, α10; concentrations: 0-1024 IU/mL; 24-96 hours) on the growth of 13 human liver cancer cell lines, the strongest anti-proliferative effects was noted In IFN-α5 subtype, and followed by α8, α10, α2, α1. 2. No synergistic growth Inhibitory effects could be recognized when IFN-α and 5-Fu were simultaneously added t o the culture of liver cancer cells. 3. Natural human IFN-α induced activation of caspase-3, -7, -8, and -9, and proteolysis of PARP in IFN-α-induced apoptosis-sensitive cell lines at various degrees. In addition, release of cytochrome C and Smac/Diablo from mitochondria into cytoplasm was identified in IFN-α-treated cells time-dependently. These findings suggest mitochondria apoptosis induction pathway is involved in the IFN-α-induced apoptosis. 4. Subcutaneous IFN-αCon1 injection (0.01, 0.1, 1μg/mouse/day; 0.01 μg/mouse = clinical dosesage) for consecutive 14 days dose-and time-dependently suppressed the HCC tumor growth in nude mice. Finally, the tumor volumes of mice received 0.01, 0.1, and 1 μg/mouse of IFN-αCon1 decreased to about 60%, 25%,and 0-10%, respectively, of control tumor volumes. The number of apoptotic cells significantly Increased and the number of blood vessels significantly decreased with the increase of IFN-αCon1 dose. 5. Synergistic effect of IFN-α plus 5-Fu was identified In nude mouse tumors. [Conclusions] These data Indicate the potential clinical application of certain types of IFN-α in the prevention and treatment of HCC.